Functionalized biodegradable triclosan monomers and oligomers for controlled release

a technology of triclosan monomers and oligomers, which is applied in the direction of solution delivery, joint implants, infusion needles, etc., can solve the problems of difficult hydrolysis and difficult polymerization in the phenolic state, and achieve the effects of improving bioavailability, high controllability, and increasing solubility

Inactive Publication Date: 2009-04-23
BEZWADA BIOMEDICAL LLC
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Benefits of technology

[0014]Applicants have found that triclosan may be functionalized with safe and biocompatible molecules such as glycolic acid, lactic acid, p-dioxanone, and / or caprolactone monomers. By careful selection of the biocompatible molecules, the hydrolysis profiles of these new functionalized triclosan compounds are more highly controllable. Other compound properties that are favorably affected include increased solubility, improved bioavailability, improved efficacy, and enhanced functionality.
[0015]The functionalization of triclosan using biocompatible molecules such as those described herein produces a hydrolysable, bioabsorbable compound. This process enhances the native value of triclosan by providing the resultant compound or combination of compounds with a specific, controlled degradation profile or range, enabling the controlled release of triclosan over an extended, controllable time range. The different controlled release profiles represent slow, moderate and / or rapid release of the active substance (triclosan). In certain embodiments this release may be targeted to one or more specific organs or parts of the body. The invention described herein greatly extends the usefulness of triclosan and provides greater control of the bioavailability of the triclosan while retaining its inherent biological properties.
[0016]Because, in certain embodiments, the functionalized triclosan compounds of the present invention retain the innate properties of the active triclosan compound, they may be used, in many instances, in applications wherein triclosan and / or triclosan compounds are typically employed. For example, they may serve as enhanced antimicrobial agents that find use, for example, in controlled release preparations, cosmetic applications, and flavors. They may also be employed, for example, in coatings for biomedical devices, such as stents, absorbable implantable devices, and / or surgical sutures, and / or for biodegradable chewing gum, nutriceuticals, or drug delivery. In addition, the active portion of the functionalized triclosan has improved bioavailability and / or increased solubility. The compounds of the present invention permit the user to better control the degradation and / or target delivery of the active triclosan component. The compounds may be further reacted and, in many cases, further polymerized, expanding their usefulness.
[0017]The present invention also relates to the discovery of functionalized triclosan compounds, and the observation that the resultant functionalized triclosan compounds and their oligomers have controllable degradation profiles, releasing the active triclosan component over a desired time range. The compounds may be used alone or in combination with with one or more other functionalized triclosan compounds of the invention as a mixture in order to extend the time range over which the active ingredient is released. The compounds may also be used in combination with absorbable polymers to further extend their usefulness by providing still greater variation in, and control of, the degradation or hydrolysis range of the functionalized triclosan compounds in the mixture.

Problems solved by technology

While triclosan compounds have various known beneficial uses, they generally are insoluble or partially soluble in water or the human body and are difficult to hydrolyze.
They are also very difficult to polymerize in the phenolic state.

Method used

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  • Functionalized biodegradable triclosan monomers and oligomers for controlled release
  • Functionalized biodegradable triclosan monomers and oligomers for controlled release
  • Functionalized biodegradable triclosan monomers and oligomers for controlled release

Examples

Experimental program
Comparison scheme
Effect test

example 1

[5-Chloro-2-(2,4-dichloro-phenoxy)-phenoxy]-acetic acid methyl ester

[0175]

[0176]To a mixture of triclosan (50 grams, 173 mmol), anhydrous K2CO3 (100 grams, 723 mmol), sodium iodide (10 grams, 66.7 mmol) and disodium phosphate (10 grams, 70 mmol) in anhydrous acetone (500 mL) was added methyl chloro acetate (30 grams, 276 mmol). The reaction mixture was refluxed for 16 hours. Acetone was distilled and water (600 mL) was added. Crude 1 was extracted into ethyl acetate, dried over Na2SO4, distilled and purified by column chromatography on silica gel using hexane as eluant to give pure 1 (45 grams, 72.1%) as a white powder. m.p: 52-53° C. IHNMR (CDCl3) δ 3.78(s, 3H, ester), 4.65 (s, 2H,OCH2), 6.72(d,1H,Ar), 6.88(m,2H,Ar), 6.92(m,1H,Ar), 7.10(m,1H,Ar), 7.42(s,1H,Ar).

example 2

2-[5-Chloro-2-(2,4-dichloro-phenoxy)-phenoxy]-propionic acid methyl ester

[0177]

[0178]To a mixture of triclosan (50 grams, 173 mmol), anhydrous K2CO3 (100 grams, 723 mmol), sodium iodide (10 grams, 66.7 mmol) and disodium phosphate (10 grams, 70 mmol) in anhydrous acetone (500 mL) was added methyl 2-chloro propionate (32.25 grams, 263 mmol). The reaction mixture was refluxed for 24 hours. Acetone was distilled and water (600 mL) was added. Crude 2 was extracted into ethyl acetate, dried over Na2SO4, distilled and purified by column chromatography on silica gel using hexane as eluant to give pure 2 (35 grams, 54%) as a syrup. IHNMR (CDCl3) δ 1.48(d,3H,CH3), 3.75(s, 3H, ester), 4.72 (q,1H,O—CH), 6.74(d,1H,Ar), 6.90(m,3H,Ar), 7.12(dd,1H,Ar), 7.42(d,1H,Ar).

example 3

6-[5-Chloro-2-(2,4-dichloro-phenoxy)-phenoxy]-hexanoic acid methyl ester

[0179]

[0180]To a mixture of triclosan (50 grams, 173 mmol), anhydrous K2CO3 (100 grams, 723 mmol), sodium iodide (10 grams, 66.7 mmol) and disodium phosphate (10 grams, 70 mmol), in anhydrous acetone (500 mL) was added methyl 6-bromo hexanoate (55 grams, 263 mmol). The reaction mixture was refluxed for 30 hours. Acetone was distilled and water (600 mL) was added. Crude 3 was extracted into ethyl acetate, dried over Na2SO4, distilled and purified by column chromatography on silica gel using hexane as eluant to give pure 3 (60 grams 90%) as a syrup. IHNMR (CDCl3) δ 1.24(m,2H,CH2), 1.58(m,2H,CH2), 1.64(m,2H,CH2), 2.24(t,2H,CH2), 3.65(s,3H, ester), 3.92 (t,2H,OCH2)), 6.60(d,1H,Ar), 6.92(m,2H,Ar), 6.96(d,1H,Ar), 7.05(d,1H,Ar), 7.42(s,1H,Ar).

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Abstract

This invention relates to the discovery of functionalized triclosan monomers and oligomers that, when incorporated into a substrate of, or applied as part of a coating to, medical devices and/or consumer products may extend the duration of antimicrobial properties to the medical devices and/or consumer products.

Description

CROSS REFERENCE TO RELATED APPLICATIONS[0001]This application claims the benefit of U.S. Application No. 60 / 975,374, filed Sep. 26, 2007, the disclosure of which is hereby incorporated herein by reference in its entirety.FIELD OF THE INVENTION[0002]This invention relates to functionalized triclosan monomers and oligomers that, when incorporated into a substrate of, or applied as part of a coating to, medical devices and / or consumer products may extend the duration of antimicrobial properties to the medical devices and / or consumer products.BACKGROUND OF THE INVENTION[0003]Triclosan is a chlorinated aromatic compound that has ether and phenol groups. Such phenols reportedly often show anti-bacterial properties. Triclosan may be used in soaps, deodorants, toothpastes mouthwashes, and cleaning supplies and is incorporated in an increasing number of consumer products, such as kitchen utensils, toys, bedding, socks, and trash bags. It has been reportedly shown as effective in reducing and...

Claims

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Application Information

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Patent Type & Authority Applications(United States)
IPC IPC(8): C08G63/00C07C69/76C07C229/38A61K47/34A61B17/03A61B17/064A61B17/56A61M5/32A61M25/00A61F2/82
CPCA61B17/064C07C235/16A61K9/08A61K9/10A61K47/12A61K47/32A61K47/34A61L27/34A61L27/54A61L29/085A61L29/16A61L31/10A61L31/16A61L2300/202A61L2300/404A61L2300/606C07C69/67C07C69/708C07C69/712A61B17/58A61P17/04A61P25/24A61P25/26A61P29/00A61P31/04A61P31/12A61P35/00A61P5/00A61P9/06A61P9/12
Inventor BEZWADA, RAO S.
Owner BEZWADA BIOMEDICAL LLC
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